Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C

Authors

  • Nicole Forestier,

    Corresponding author
    1. Saarland University Hospital, Homburg, Germany
    2. J.W. Goethe University Hospital, Frankfurt, Germany
    • Saarland University Hospital, Homburg, Germany
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    • These authors contributed equally to this study.

    • fax: +49-6841-162-3583

  • Hendrik W. Reesink,

    1. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands
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    • Potential conflict of interest: Dr. Zeuzem is a consultant of Roche and Vertex. He is on the speakers' bureau of Roche and received grants from Roche. He also received grants from Vertex. Dr. Purdy is an employee of Vertex Pharmaceuticals. Dr. Chu owns stock in Vertex. Dr. Reesink received grants from Vertex. Dr. McNair is an employee of Vertex Pharmaceuticals. Dr. Kieffer owns stock and is an employee of Vertex.

    • These authors contributed equally to this study.

  • Christine J. Weegink,

    1. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands
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  • Lindsay McNair,

    1. Vertex Pharmaceuticals Incorporated, Cambridge, MA
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    • Potential conflict of interest: Dr. Zeuzem is a consultant of Roche and Vertex. He is on the speakers' bureau of Roche and received grants from Roche. He also received grants from Vertex. Dr. Purdy is an employee of Vertex Pharmaceuticals. Dr. Chu owns stock in Vertex. Dr. Reesink received grants from Vertex. Dr. McNair is an employee of Vertex Pharmaceuticals. Dr. Kieffer owns stock and is an employee of Vertex.

  • Tara L. Kieffer,

    1. Vertex Pharmaceuticals Incorporated, Cambridge, MA
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  • Hui-May Chu,

    1. Vertex Pharmaceuticals Incorporated, Cambridge, MA
    Current affiliation:
    1. Anoixis Corp., Natick, MA
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    • Potential conflict of interest: Dr. Zeuzem is a consultant of Roche and Vertex. He is on the speakers' bureau of Roche and received grants from Roche. He also received grants from Vertex. Dr. Purdy is an employee of Vertex Pharmaceuticals. Dr. Chu owns stock in Vertex. Dr. Reesink received grants from Vertex. Dr. McNair is an employee of Vertex Pharmaceuticals. Dr. Kieffer owns stock and is an employee of Vertex.

  • Susan Purdy,

    1. Vertex Pharmaceuticals Incorporated, Cambridge, MA
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    • Potential conflict of interest: Dr. Zeuzem is a consultant of Roche and Vertex. He is on the speakers' bureau of Roche and received grants from Roche. He also received grants from Vertex. Dr. Purdy is an employee of Vertex Pharmaceuticals. Dr. Chu owns stock in Vertex. Dr. Reesink received grants from Vertex. Dr. McNair is an employee of Vertex Pharmaceuticals. Dr. Kieffer owns stock and is an employee of Vertex.

  • Peter L.M. Jansen,

    1. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands
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  • Stefan Zeuzem

    1. Saarland University Hospital, Homburg, Germany
    2. J.W. Goethe University Hospital, Frankfurt, Germany
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    • Potential conflict of interest: Dr. Zeuzem is a consultant of Roche and Vertex. He is on the speakers' bureau of Roche and received grants from Roche. He also received grants from Vertex. Dr. Purdy is an employee of Vertex Pharmaceuticals. Dr. Chu owns stock in Vertex. Dr. Reesink received grants from Vertex. Dr. McNair is an employee of Vertex Pharmaceuticals. Dr. Kieffer owns stock and is an employee of Vertex.


  • See Editorial on Page 615

Abstract

Telaprevir (VX-950), an inhibitor of the hepatitis C virus (HCV) NS3/4A protease, substantially decreased plasma HCV RNA levels in a prior clinical study. The present study evaluated viral kinetics and safety during dosing with telaprevir alone and in combination with peginterferon alfa-2a for 14 days. Previously untreated patients with genotype 1 hepatitis C were randomized to receive placebo and peginterferon alfa-2a (n = 4); telaprevir (n = 8); or telaprevir and peginterferon alfa-2a (n = 8). Telaprevir was given as 750 mg oral doses every 8 hours; peginterferon alfa-2a was given as weekly 180 μg subcutaneous injections. The median change in HCV RNA from baseline to day 15 was −1.09 log10 (range, −2.08 to −0.46) in the placebo and peginterferon alfa-2a group; −3.99 log10 (range, −5.28 to −1.26) in the telaprevir group, and −5.49 log10 (range, −6.54 to −4.30) in the telaprevir and peginterferon alfa-2a group. Day 15 HCV RNA levels were undetectable in 4 patients who received telaprevir and peginterferon alfa-2a and in 1 patient who received telaprevir alone. No viral breakthrough occurred in patients who received telaprevir and peginterferon alfa-2a. The majority of adverse events were mild. There were no serious adverse events or premature discontinuations. Twelve weeks after starting off-study standard therapy, HCV RNA was undetectable in all 8 patients in the telaprevir and peginterferon alfa-2a group, 5 patients in the telaprevir group, and 1 patient in the placebo and peginterferon alfa-2a group. Conclusion: This study confirmed the substantial antiviral effects of telaprevir and showed an increased antiviral effect of telaprevir combined with peginterferon alfa-2a. (HEPATOLOGY 2007;46:640–648.)

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